Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer.
Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer.
复制标题
通过罗格列酮恢复脂联素可改善肺癌小鼠的组织消耗。
DOI：
10.1101/2023.07.31.551241
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Goncalves,AndMarcusD
中科院分区：
文献类型：
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作者：
Langer,HenningTim;Ramsamooj,Shakti;Dantas,Ezequiel;Murthy,Anirudh;Ahmed,Mujmmail;Hwang,Seo-Kyoung;Grover,Rahul;Pozovskiy,Rita;Liang,RogerJ;Queiroz,AndreLima;Brown,JustinC;White,EileenP;Janowitz,Tobias;Goncalves,AndMarcusD
AimTo研究肺癌临床前模型中癌症相关恶病质综合征（CACS）的全身调节因子，以确定组织wasting.MethodsUsing Kras/Lkb 1（KL）小鼠模型的治疗靶点，我们发现CACS与直接影响骨骼肌稳态的白色脂肪组织（WAT）功能障碍相关。WAT转录组显示脂肪生成减少的证据，并且，我们发现循环脂联素水平较低。为了保持脂肪生成和恢复脂联素水平，我们用PPAR-γ激动剂罗格列酮治疗小鼠，罗格列酮治疗增加血清脂联素水平，延迟体重减轻，并保留骨骼肌和脂肪组织质量，相比，车辆治疗小鼠。罗格列酮对肌肉质量的保护与AMPK和AKT活性的增加有关。同样，肌细胞中脂联素受体的激活增加了AMPK活性，合成代谢信号和蛋白质合成。ConclusionOur data suggests，PPAR-γ激动剂可能是一种有用的辅助治疗，以保护肺癌组织块。
AimTo investigate systemic regulators of the cancer‐associated cachexia syndrome (CACS) in a pre‐clinical model for lung cancer with the goal to identify therapeutic targets for tissue wasting.MethodsUsing the Kras/Lkb1 (KL) mouse model, we found that CACS is associated with white adipose tissue (WAT) dysfunction that directly affects skeletal muscle homeostasis. WAT transcriptomes showed evidence of reduced adipogenesis, and, in agreement, we found low levels of circulating adiponectin. To preserve adipogenesis and restore adiponectin levels, we treated mice with the PPAR‐γ agonist, rosiglitazone.ResultsRosiglitazone treatment increased serum adiponectin levels, delayed weight loss, and preserved skeletal muscle and adipose tissue mass, as compared to vehicle‐treated mice. The preservation of muscle mass with rosiglitazone was associated with increases in AMPK and AKT activity. Similarly, activation of the adiponectin receptors in muscle cells increased AMPK activity, anabolic signaling, and protein synthesis.ConclusionOur data suggest that PPAR‐γ agonists may be a useful adjuvant therapy to preserve tissue mass in lung cancer.